Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF
Previous studies suggest that genetic variants within genes affecting the circadian rhythm influence the development of posttraumatic stress symptoms (PTSS). In the present study, we used data from three emergency care-based cohorts to search genetic variants in circadian pathway genes previously as...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00597/full |
| _version_ | 1819053870598324224 |
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| author | Sarah D. Linnstaedt Sarah D. Linnstaedt Yue Pan Yue Pan Matthew C. Mauck Matthew C. Mauck Jenyth Sullivan Christine Y. Zhou Lindsey Jung Lindsey Jung Cathleen A. Rueckeis Jameson D. Blount Matthew S. Carson Andrew S. Tungate Michael C. Kurz Phyllis L. Hendry Christopher Lewandowski Teresa D'Anza Elizabeth Datner Kathy Bell Megan Lechner Jeffrey W. Shupp Bruce A. Cairns Samuel A. McLean Samuel A. McLean Samuel A. McLean |
| author_facet | Sarah D. Linnstaedt Sarah D. Linnstaedt Yue Pan Yue Pan Matthew C. Mauck Matthew C. Mauck Jenyth Sullivan Christine Y. Zhou Lindsey Jung Lindsey Jung Cathleen A. Rueckeis Jameson D. Blount Matthew S. Carson Andrew S. Tungate Michael C. Kurz Phyllis L. Hendry Christopher Lewandowski Teresa D'Anza Elizabeth Datner Kathy Bell Megan Lechner Jeffrey W. Shupp Bruce A. Cairns Samuel A. McLean Samuel A. McLean Samuel A. McLean |
| author_sort | Sarah D. Linnstaedt |
| collection | DOAJ |
| description | Previous studies suggest that genetic variants within genes affecting the circadian rhythm influence the development of posttraumatic stress symptoms (PTSS). In the present study, we used data from three emergency care-based cohorts to search genetic variants in circadian pathway genes previously associated with neuropsychiatric disorders for variants that influence PTSS severity. The three cohorts used included a discovery cohort of African American men and women enrolled following motor vehicle collision (n = 907) and two replication cohorts: one of multi-ethnic women enrolled following sexual assault (n = 274) and one of multi-ethnic men and women enrolled following major thermal burn injury (n = 68). DNA and RNA were collected from trauma survivors at the time of initial assessment. Validated questionnaires were used to assess peritraumatic distress severity and to assess PTSS severity 6 weeks, 6 months, and 1 year following trauma exposure. Thirty-one genetic variants from circadian rhythm genes were selected for analyses, and main effect and potential gene*stress and gene*sex interactions were evaluated. Secondary analyses assessed whether associated genetic variants affected mRNA expression levels. We found that six genetic variants across five circadian rhythm-associated genes predicted PTSS outcomes following motor vehicle collision (p < 0.05), but only two of these variants survived adjustment for multiple comparisons (False Discovery Rate < 5%). The strongest of these associations, an interaction between the PAR-zip transcription factor, thyrotroph embryonic factor (TEF) variant rs5758324 and peritraumatic distress, predicted PTSS development in all three cohorts. Further analysis of genetic variants in the genetic region surrounding TEFrs5758324 (±125,000 nucleotides) indicated that this allele showed the strongest association. Further, TEF RNA expression levels (determined via RNA-seq) were positively associated with PTSS severity in distressed individuals with at least one copy of the TEFrs5758324 minor allele. These results suggest that rs5758324 genetic variant in TEF, a regulator of clock-controlled genes and key mediator of the core circadian rhythm, influence PTSS severity in a stress-dependent manner. |
| first_indexed | 2024-12-21T12:42:36Z |
| format | Article |
| id | doaj.art-69dacb668c8c4169aa985b5092a74124 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-21T12:42:36Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Psychiatry |
| spelling | doaj.art-69dacb668c8c4169aa985b5092a741242022-12-21T19:03:44ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402018-11-01910.3389/fpsyt.2018.00597414553Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEFSarah D. Linnstaedt0Sarah D. Linnstaedt1Yue Pan2Yue Pan3Matthew C. Mauck4Matthew C. Mauck5Jenyth Sullivan6Christine Y. Zhou7Lindsey Jung8Lindsey Jung9Cathleen A. Rueckeis10Jameson D. Blount11Matthew S. Carson12Andrew S. Tungate13Michael C. Kurz14Phyllis L. Hendry15Christopher Lewandowski16Teresa D'Anza17Elizabeth Datner18Kathy Bell19Megan Lechner20Jeffrey W. Shupp21Bruce A. Cairns22Samuel A. McLean23Samuel A. McLean24Samuel A. McLean25Institute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Anesthesiology, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Anesthesiology, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Emergency Medicine, University of Alabama School of Medicine, Birmingham, AL, United StatesDepartment of Emergency Medicine, University of Florida College of Medicine, Jacksonville, FL, United StatesDepartment of Emergency Medicine, Henry Ford Hospital, Detroit, MI, United StatesAlbuquerque Sexual Assault Nurse Examiner Collaborative, Albuquerque, NM, United StatesDepartment of Emergency Medicine, Albert Einstein Medical Center, Philadelphia, PA, United States0Forensic Nursing Program, Tulsa Police Department, Tulsa, OK, United States1Forensic Nursing Program, Memorial Health System, Colorado Springs, CO, United States2Department of Surgery, The Burn Center, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, DC, United States3Jaycee Burn Center, University of North Carolina, Chapel Hill, NC, United StatesInstitute for Trauma Recovery, University of North Carolina, Chapel Hill, NC, United StatesDepartment of Anesthesiology, University of North Carolina, Chapel Hill, NC, United States4Department of Emergency Medicine, University of North Carolina, Chapel Hill, NC, United StatesPrevious studies suggest that genetic variants within genes affecting the circadian rhythm influence the development of posttraumatic stress symptoms (PTSS). In the present study, we used data from three emergency care-based cohorts to search genetic variants in circadian pathway genes previously associated with neuropsychiatric disorders for variants that influence PTSS severity. The three cohorts used included a discovery cohort of African American men and women enrolled following motor vehicle collision (n = 907) and two replication cohorts: one of multi-ethnic women enrolled following sexual assault (n = 274) and one of multi-ethnic men and women enrolled following major thermal burn injury (n = 68). DNA and RNA were collected from trauma survivors at the time of initial assessment. Validated questionnaires were used to assess peritraumatic distress severity and to assess PTSS severity 6 weeks, 6 months, and 1 year following trauma exposure. Thirty-one genetic variants from circadian rhythm genes were selected for analyses, and main effect and potential gene*stress and gene*sex interactions were evaluated. Secondary analyses assessed whether associated genetic variants affected mRNA expression levels. We found that six genetic variants across five circadian rhythm-associated genes predicted PTSS outcomes following motor vehicle collision (p < 0.05), but only two of these variants survived adjustment for multiple comparisons (False Discovery Rate < 5%). The strongest of these associations, an interaction between the PAR-zip transcription factor, thyrotroph embryonic factor (TEF) variant rs5758324 and peritraumatic distress, predicted PTSS development in all three cohorts. Further analysis of genetic variants in the genetic region surrounding TEFrs5758324 (±125,000 nucleotides) indicated that this allele showed the strongest association. Further, TEF RNA expression levels (determined via RNA-seq) were positively associated with PTSS severity in distressed individuals with at least one copy of the TEFrs5758324 minor allele. These results suggest that rs5758324 genetic variant in TEF, a regulator of clock-controlled genes and key mediator of the core circadian rhythm, influence PTSS severity in a stress-dependent manner.https://www.frontiersin.org/article/10.3389/fpsyt.2018.00597/fullPTSDgenetic polymorphismcircadian rhythmtraumaTEFRNA |
| spellingShingle | Sarah D. Linnstaedt Sarah D. Linnstaedt Yue Pan Yue Pan Matthew C. Mauck Matthew C. Mauck Jenyth Sullivan Christine Y. Zhou Lindsey Jung Lindsey Jung Cathleen A. Rueckeis Jameson D. Blount Matthew S. Carson Andrew S. Tungate Michael C. Kurz Phyllis L. Hendry Christopher Lewandowski Teresa D'Anza Elizabeth Datner Kathy Bell Megan Lechner Jeffrey W. Shupp Bruce A. Cairns Samuel A. McLean Samuel A. McLean Samuel A. McLean Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF Frontiers in Psychiatry PTSD genetic polymorphism circadian rhythm trauma TEF RNA |
| title | Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF |
| title_full | Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF |
| title_fullStr | Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF |
| title_full_unstemmed | Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF |
| title_short | Evaluation of the Association Between Genetic Variants in Circadian Rhythm Genes and Posttraumatic Stress Symptoms Identifies a Potential Functional Allele in the Transcription Factor TEF |
| title_sort | evaluation of the association between genetic variants in circadian rhythm genes and posttraumatic stress symptoms identifies a potential functional allele in the transcription factor tef |
| topic | PTSD genetic polymorphism circadian rhythm trauma TEF RNA |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00597/full |
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